US6635256B1ExpiredUtility
Glycoprotein hormone compositions comprising two β subunits and methods of use thereof
Est. expiryOct 19, 2018(expired)· nominal 20-yr term from priority
A61P 43/00A61P 15/00A61P 15/08C07K 2319/00A61K 38/24A61K 38/00C07K 14/59
53
PatentIndex Score
10
Cited by
34
References
30
Claims
Abstract
Forms of differentially acting glycoprotein hormones are disclosed. These compositions are of the formulawherein each of beta<1 >and beta<2 >has the amino acid sequence of the beta subunit of a vertebrate glycoprotein hormone or a variant of said amino acid sequence as variants are defined herein. "alpha" designates the a subunit of a vertebrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that spaces the beta<1 >and beta<2 >subunits at appropriate distances from the alpha subunit and from each other. "≈" is a noncovalent link. Each of m and n is independently 0 or 1.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A method to provide a subject with glycoprotein hormone activities which method comprises administering to a subject in need of said activities a composition of the formula:
β 2 ≈α-(linker) m -β 1 (1); or
β 1 -(linker) m -α≈β 2 (2)
wherein each of β 1 and β 2 has the amino acid sequence of the β subunit of a vertebrate glycoprotein hormone, or a variant thereof;
“α” has the amino acid sequence of the α subunit of a vertebrate glycoprotein hormone or a variant thereof;
“linker” is a linker moiety; and
“≈” is a noncovalent link between α and β 2 ;
m is 0 or 1;
wherein each of β 1 and β 2 is the native β subunit of the same glycoprotein hormone or a variant thereof.
2. The method of claim 1 wherein β 1 and β 2 are native β subunits.
3. The method of claim 1 wherein β 1 and β 2 exhibit different biological half-lives.
4. The method of claim 1 wherein one of β 1 and β 2 confers agonist activity and the other confers antagonist activity.
5. The method of claim 4 , wherein β 1 is FSHβ or a variant thereof and β 2 is FSHβ or a variant thereof.
6. The method of claim 4 , wherein β 1 is LHβ or a variant thereof and β 2 is LHβ or a variant thereof.
7. The method of claim 4 , wherein β 1 is TSHβ or a variant thereof and β 2 is TSHβ or a variant thereof.
8. The method of claim 4 , wherein β 1 is CGβ or a variant thereof and β 2 is CGβ or a variant thereof.
9. The method of claim 1 wherein said subject is being treated to enhance fertility.
10. The method of claim 9 wherein
both β 1 and β 2 confer FSH agonist activity on said composition; or
both β 1 and β 2 confer CG agonist activity; or
both β 1 and β 2 confer LH antagonist activity.
11. The method of claim 1 wherein said subject is being treated so as to become infertile or to remain infertile.
12. The method of claim 11 wherein both β 1 and β 2 confer FSH antagonist activity on said composition; or
wherein both β 1 and β 2 confer CG antagonist activity; or
wherein both β 1 and β 2 confer LH agonist activity.
13. The method of claim 1 wherein the subject is in need of treatment for polycystic ovarian disease.
14. The method of claim 13 wherein
both β 1 and β 2 confer FSH agonist activity; or
both β 1 and β 2 confer LH antagonist activity.
15. The method of claim 1 , wherein both of β 1 and β 2 confer agonist activity.
16. The method of claim 15 , wherein β 1 is FSHβ or a variant thereof and β 2 is FSHβ or a variant thereof.
17. The method of claim 15 , wherein β 1 is LHβ or a variant thereof and β 2 is LHβ or a variant thereof.
18. The method of claim 15 , wherein β 1 is TSHβ or a variant thereof and β 2 is TSHβ or a variant thereof.
19. The method of claim 15 , wherein β 1 is CGβ or a variant thereof and β 2 is CGβ or a variant thereof.
20. The method of claim 1 , where both of β 1 and β 2 confer antagonist activity.
21. The method of claim 20 , wherein β 1 is an FSHβ variant and β 2 is an FSHβ variant.
22. The method of claim 20 , wherein β 1 is an LHβ variant and β 2 is an LHβ variant.
23. The method of claim 20 , wherein β 1 is a TSHβ variant and β 2 is a TSHβ variant.
24. The method of claim 20 , wherein β 1 is a CGβ variant and β 2 is a CGβ variant.
25. A glycosylated or nonglycosylated composition of the formula
β 2 ≈α-(linker) m -β 1 (1); or
β 1 -(linker) m -α≈β 2 (2)
wherein each of β 1 and β 2 has the amino acid sequence of the β subunit of a vertebrate glycoprotein hormone, or a variant thereof;
“α” has the amino acid sequence of the a subunit of a vertebrate glycoprotein hormone or a variant thereof;
“linker” is a linker moiety; and
“≈” is a noncovalent link between α and β 2 ;
m is 0 or 1;
wherein each of β 1 and β 2 is the native β subunit of the same glycoprotein hormone or a variant thereof.
26. The composition of claim 25 , wherein β 1 is FSHβ or a variant thereof and β 2 is FSHβ or a variant thereof.
27. The composition of claim 25 , wherein β 1 is LHβ or a variant thereof and β 2 is LHβ or a variant thereof.
28. The composition of claim 25 , wherein β 1 is TSHβ or a variant thereof and β 2 is TSHβ or a variant thereof.
29. The composition of claim 25 , wherein β 1 is CGβ or a variant thereof and β 2 is CGβ or a variant thereof.
30. A pharmaceutical composition which regulates the glycoprotein hormone concentrations in a mammal which comprises an effective amount of the composition of the formula
β 2 ≈α-(linker) m -β 1 (1); or
β 1 -(linker) m -α≈β 2 (2)
in admixture with at least one pharmaceutically acceptable excipient; and
wherein each of β 1 and β 2 has the amino acid sequence of the β subunit of a vertebrate glycoprotein hormone, or a variant thereof;
“α” has the amino acid sequence of the α subunit of a vertebrate glycoprotein hormone or a variant thereof;
“linker” is a linker moiety; and
“≈” is a noncovalent link between α and β 2 ;
each of m and n is independently 0 or 1;
wherein each of β 1 and β 2 is the native β subunit of the same glycoprotein hormone or a variant thereof.Cited by (0)
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